The experiments in this proposal are designed to investigate the interactions between sensory nerves and their target organs during development. The model system for these studies is the fungiform papillae (FP) and taste buds (TBs) on the embryonic rat tongue. Each papilla is innervated by two sensory nerves, the chorda tympani (CT), which innervates TBs exclusively, and the lingual, a branch of the trigeminal nerve, which provides somatosensory innervation to the papilla and the entire mucosa of the anterior part of the tongue, but is essentially excluded from the TB. We plan to use a novel approach to study the development of TBs and papillae with minimum perturbation of the tissue. 1) We shall use in utero surgery to interrupt the CT before it reaches the tongue epithelium, and immunological means to inhibit development of the trigeminal nerve, to determine how removal of either or both nerves affects differentiation of the FP and their TB. 2) We shall do immunohistochemical studies on the extracellular matrix of the tongue before and during nerve growth to determine whether the matrix is organized in a way that might provide a pathway for the nerves to follow as they grow through the body of the tongue toward the mucosa. 3) We shall do immunohistochemical studies on the FP of rat tongue during development to determine whether nerve growth factor (NGF) or NGF-receptors are differentially present in the FP epithelium, TB and nerves. The rationale for this is based on the observation that trigeminal ganglion cells require NGF for their maintenance, whereas CT ganglion cells do not. It is possible that the reason why the nerves are differentially distributed to different parts of the FP is that the respective neurotrophic factors, such as NGF, required by each nerve are made by those epithelial cells that they innervate, i.e., perigemmal cells for the lingual and TB cells for the CT nerves.